Pfizer Oncology, 50 Pequot Ave. MS6025-A3266, New London, CT 06320, USA.
Curr Drug Targets. 2009 Oct;10(10):923-36. doi: 10.2174/138945009789577945.
The insulin-like growth factor I receptor (IGF-IR) pathway plays a major role in cancer growth, tumor cell survival and resistance to therapy. Ancillary evidence that targeting the IGF-IR may be useful in the treatment of cancer has been accumulating for almost two decades. Today, more than two dozen compounds have been developed and clinical trials are underway for at least 12 of those. The ability to pharmacologically control the IGF-IR pathway holds not only promising therapeutic implications but also the possibility to gather a better understanding of the role of the IGF axis in tumor initiation and progression. This review focuses on the preclinical rationale for targeting the IGF-IR and other components of the IGF-I system, early clinical results observed to date, biomarker approaches employed and the lessons from these early results for future study design. Early clinical trials reveal an acceptable safety profile together with pharmacodynamic evidence of receptor targeting. Instances of single-agent activity during phase I evaluations have been well documented and a recently reported randomized phase II study indicates that co-administration of an anti-IGF-IR antibody with chemotherapy improves objective response rate and progression-free survival in non-small cell lung cancer patients. These early results support ongoing research across a broad range of cancer indications.
胰岛素样生长因子 I 受体 (IGF-IR) 途径在癌症生长、肿瘤细胞存活和对治疗的耐药性方面发挥着重要作用。近二十年来，越来越多的辅助证据表明，针对 IGF-IR 的治疗可能对癌症治疗有用。如今，已经开发出了二十多种化合物，并且至少有 12 种化合物正在进行临床试验。通过药理学控制 IGF-IR 途径不仅具有有前途的治疗意义，而且还有可能更好地了解 IGF 轴在肿瘤发生和进展中的作用。这篇综述重点介绍了针对 IGF-IR 及 IGF-I 系统其他成分的临床前基本原理、迄今为止观察到的早期临床结果、所采用的生物标志物方法以及这些早期结果对未来研究设计的启示。早期临床试验揭示了可接受的安全性概况以及受体靶向的药效学证据。在 I 期评估期间，单药治疗的实例已有充分记录，最近报告的一项随机 II 期研究表明，在非小细胞肺癌患者中，抗 IGF-IR 抗体与化疗联合使用可提高客观缓解率和无进展生存期。这些早期结果支持在广泛的癌症适应症中开展持续的研究。
